Any feedback?
Please rate this page
(literature.php)
(0/150)

BRENDA support

Literature summary extracted from

  • Amsailale, R.; Van Den Neste, E.; Arts, A.; Starczewska, E.; Bontemps, F.; Smal, C.
    Phosphorylation of deoxycytidine kinase on Ser-74: impact on kinetic properties and nucleoside analog activation in cancer cells (2012), Biochem. Pharmacol., 84, 43-51.
    View publication on PubMed

Activating Compound

EC Number Activating Compound Comment Organism Structure
2.7.1.74 aphidicolin increases dCK activity via Ser74 phosphorylation, effect of aphidicolin treatment on dCK activity in leukemic cells with substrate deoxycytidine and cladribine and other substrates, overview Homo sapiens

Application

EC Number Application Comment Organism
2.7.1.74 additional information deoxycytidine kinase is a key enzyme in the activation of several therapeutic nucleoside analogues Homo sapiens

Protein Variants

EC Number Protein Variants Comment Organism
2.7.1.74 S74E site-directed mutagenesis, the mutation sensitizes the enzyme to feedback inhibition by dCTP, regardless of the phosphoryl donor. Mimicking Ser74 phosphorylation by a S74E mutation increases the enzyme activity toward pyrimidine analogues. The S74E mutation increased the kcat for cladribine by 8 or 3fold, depending on whether the phosphoryl donor was ATP or UTP, for clofarabine by about 2fold with both ATP and UTP, and for fludarabine by 2fold, but only with UTP Homo sapiens

Inhibitors

EC Number Inhibitors Comment Organism Structure
2.7.1.74 dCTP a potent inhibitor of the enzyme when ATP is the phosphoryl donor, but a relatively weak inhibitor when the enzyme activity is measured with UTP as the phosphoryl donor. Inhibition is higher with respect to cladribine than deoxycytidine Homo sapiens

KM Value [mM]

EC Number KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
2.7.1.74 0.00007
-
 deoxycytidine pH 7.6, 37°C, wild-type enzyme, with co-substrate ATP Homo sapiens
2.7.1.74 0.00009
-
 deoxycytidine pH 7.6, 37°C, wild-type enzyme, with co-substrate UTP Homo sapiens
2.7.1.74 0.00018
-
 deoxycytidine pH 7.6, 37°C, enzyme mutant S74E, with co-substrate UTP Homo sapiens
2.7.1.74 0.00027
-
 deoxycytidine pH 7.6, 37°C, enzyme mutant S74E, with co-substrate ATP Homo sapiens
2.7.1.74 0.00065
-
 cladribine pH 7.6, 37°C, wild-type enzyme, with co-substrate UTP Homo sapiens
2.7.1.74 0.0016
-
 cladribine pH 7.6, 37°C, enzyme mutant S74E, with co-substrate UTP Homo sapiens
2.7.1.74 0.0024
-
 cladribine pH 7.6, 37°C, wild-type enzyme, with co-substrate ATP Homo sapiens
2.7.1.74 0.0087
-
 clofarabine pH 7.6, 37°C, wild-type enzyme, with co-substrate UTP Homo sapiens
2.7.1.74 0.0155
-
 cladribine pH 7.6, 37°C, enzyme mutant S74E, with co-substrate ATP Homo sapiens
2.7.1.74 0.0155
-
 clofarabine pH 7.6, 37°C, enzyme mutant S74E, with co-substrate UTP Homo sapiens
2.7.1.74 0.022
-
 clofarabine pH 7.6, 37°C, wild-type enzyme, with co-substrate ATP Homo sapiens
2.7.1.74 0.028
-
 fludarabine pH 7.6, 37°C, wild-type enzyme, with co-substrate UTP Homo sapiens
2.7.1.74 0.0325
-
 clofarabine pH 7.6, 37°C, enzyme mutant S74E, with co-substrate ATP Homo sapiens
2.7.1.74 0.142
-
 fludarabine pH 7.6, 37°C, enzyme mutant S74E, with co-substrate UTP Homo sapiens
2.7.1.74 0.45
-
 fludarabine pH 7.6, 37°C, wild-type enzyme, with co-substrate ATP Homo sapiens
2.7.1.74 0.551
-
 fludarabine pH 7.6, 37°C, enzyme mutant S74E, with co-substrate ATP Homo sapiens

Localization

EC Number Localization Comment Organism GeneOntology No. Textmining
2.7.1.74 cytosol
-
 Homo sapiens 5829
-

Metals/Ions

EC Number Metals/Ions Comment Organism Structure
2.7.1.74 Mg2+ required Homo sapiens

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
2.7.1.74 ATP + cladribine Homo sapiens
-
 ADP + cladribine 5'-phosphate
-
 ?
2.7.1.74 ATP + clofarabine Homo sapiens
-
 ADP + clofarabine 5'-phosphate
-
 ?
2.7.1.74 ATP + deoxyadenosine Homo sapiens
-
 ADP + dAMP
-
 ?
2.7.1.74 ATP + deoxycytidine Homo sapiens
-
 ADP + dCMP
-
 ?
2.7.1.74 ATP + deoxyguanosine Homo sapiens
-
 ADP + dGMP
-
 ?
2.7.1.74 ATP + fludarabine Homo sapiens
-
 ADP + fludarabine 5'-phosphate
-
 ?
2.7.1.74 UTP + cladribine Homo sapiens
-
 UDP + cladribine 5'-phosphate
-
 ?
2.7.1.74 UTP + clofarabine Homo sapiens
-
 UDP + clofarabine 5'-phosphate
-
 ?
2.7.1.74 UTP + deoxyadenosine Homo sapiens
-
 UDP + dAMP
-
 ?
2.7.1.74 UTP + deoxycytidine Homo sapiens
-
 UDP + dCMP
-
 ?
2.7.1.74 UTP + deoxyguanosine Homo sapiens
-
 UDP + dGMP
-
 ?
2.7.1.74 UTP + fludarabine Homo sapiens
-
 UDP + phospho-fludarabine
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
2.7.1.74 Homo sapiens
-
-
-

Posttranslational Modification

EC Number Posttranslational Modification Comment Organism
2.7.1.74 phosphoprotein phosphorylation of deoxycytidine kinase on Ser74 increases the enzyme activity, increasing dCK activity via Ser74 phosphorylation, e.g. by aphidicolin, can enhance the intracellular activation of some nucleoside analogs, like gemcitabine, but not of cladribine or fludarabine, overview Homo sapiens

Source Tissue

EC Number Source Tissue Comment Organism Textmining
2.7.1.74 chronic lymphocytic leukemia cell
-
 Homo sapiens
-
2.7.1.74 HCT-116 cell
-
 Homo sapiens
-
2.7.1.74 HT-29 cell
-
 Homo sapiens
-
2.7.1.74 leukemia cell
-
 Homo sapiens
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
2.7.1.74 ATP + cladribine
-
 Homo sapiens ADP + cladribine 5'-phosphate
-
 ?
2.7.1.74 ATP + clofarabine
-
 Homo sapiens ADP + clofarabine 5'-phosphate
-
 ?
2.7.1.74 ATP + deoxyadenosine
-
 Homo sapiens ADP + dAMP
-
 ?
2.7.1.74 ATP + deoxycytidine
-
 Homo sapiens ADP + dCMP
-
 ?
2.7.1.74 ATP + deoxyguanosine
-
 Homo sapiens ADP + dGMP
-
 ?
2.7.1.74 ATP + fludarabine
-
 Homo sapiens ADP + fludarabine 5'-phosphate
-
 ?
2.7.1.74 additional information deoxycytidine kinase shows broad substrate specificity, catalyzing the phosphorylation of deoxycytidine, deoxyadenosine, and deoxyguanosine with ATP or UTP as phosphoryl donor Homo sapiens ?
-
 ?
2.7.1.74 UTP + cladribine
-
 Homo sapiens UDP + cladribine 5'-phosphate
-
 ?
2.7.1.74 UTP + clofarabine
-
 Homo sapiens UDP + clofarabine 5'-phosphate
-
 ?
2.7.1.74 UTP + deoxyadenosine
-
 Homo sapiens UDP + dAMP
-
 ?
2.7.1.74 UTP + deoxycytidine
-
 Homo sapiens UDP + dCMP
-
 ?
2.7.1.74 UTP + deoxyguanosine
-
 Homo sapiens UDP + dGMP
-
 ?
2.7.1.74 UTP + fludarabine
-
 Homo sapiens UDP + phospho-fludarabine
-
 ?

Synonyms

EC Number Synonyms Comment Organism
2.7.1.74 dCK
-
 Homo sapiens

Temperature Optimum [°C]

EC Number Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
2.7.1.74 37
-
 assay at Homo sapiens

Turnover Number [1/s]

EC Number Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
2.7.1.74 0.015
-
 deoxycytidine pH 7.6, 37°C, wild-type enzyme, with co-substrate ATP Homo sapiens
2.7.1.74 0.021
-
 deoxycytidine pH 7.6, 37°C, wild-type enzyme, with co-substrate UTP Homo sapiens
2.7.1.74 0.0804
-
 cladribine pH 7.6, 37°C, wild-type enzyme, with co-substrate UTP Homo sapiens
2.7.1.74 0.123
-
 deoxycytidine pH 7.6, 37°C, enzyme mutant S74E, with co-substrate UTP Homo sapiens
2.7.1.74 0.172
-
 cladribine pH 7.6, 37°C, wild-type enzyme, with co-substrate ATP Homo sapiens
2.7.1.74 0.177
-
 fludarabine pH 7.6, 37°C, wild-type enzyme, with co-substrate UTP Homo sapiens
2.7.1.74 0.183
-
 deoxycytidine pH 7.6, 37°C, enzyme mutant S74E, with co-substrate ATP Homo sapiens
2.7.1.74 0.211
-
 cladribine pH 7.6, 37°C, enzyme mutant S74E, with co-substrate UTP Homo sapiens
2.7.1.74 0.363
-
 fludarabine pH 7.6, 37°C, enzyme mutant S74E, with co-substrate UTP Homo sapiens
2.7.1.74 0.486
-
 clofarabine pH 7.6, 37°C, wild-type enzyme, with co-substrate UTP Homo sapiens
2.7.1.74 0.88
-
 clofarabine pH 7.6, 37°C, enzyme mutant S74E, with co-substrate UTP Homo sapiens
2.7.1.74 1.005
-
 fludarabine pH 7.6, 37°C, enzyme mutant S74E, with co-substrate ATP Homo sapiens
2.7.1.74 1.11
-
 clofarabine pH 7.6, 37°C, wild-type enzyme, with co-substrate ATP Homo sapiens
2.7.1.74 1.334
-
 fludarabine pH 7.6, 37°C, wild-type enzyme, with co-substrate ATP Homo sapiens
2.7.1.74 1.386
-
 cladribine pH 7.6, 37°C, enzyme mutant S74E, with co-substrate ATP Homo sapiens
2.7.1.74 2.45
-
 clofarabine pH 7.6, 37°C, enzyme mutant S74E, with co-substrate ATP Homo sapiens

pH Optimum

EC Number pH Optimum Minimum pH Optimum Maximum Comment Organism
2.7.1.74 7.6
-
 assay at Homo sapiens

Cofactor

EC Number Cofactor Comment Organism Structure
2.7.1.74 ATP
-
 Homo sapiens
2.7.1.74 UTP
-
 Homo sapiens

Ki Value [mM]

EC Number Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
2.7.1.74 0.0015
-
 dCTP pH 7.6, 37°C, enzyme mutant S74E, with substrates cladribine and ATP, mixed inhibition Homo sapiens
2.7.1.74 0.0029
-
 dCTP pH 7.6, 37°C, enzyme mutant S74E, with substrates deoxycytidine and ATP, mixed inhibition Homo sapiens
2.7.1.74 0.0058
-
 dCTP pH 7.6, 37°C, wild-type enzyme, with substrates cladribine and ATP, mixed inhibition Homo sapiens
2.7.1.74 0.027
-
 dCTP pH 7.6, 37°C, enzyme mutant S74E, with substrates cladribine and UTP, uncompetitive inhibition Homo sapiens
2.7.1.74 0.03
-
 dCTP pH 7.6, 37°C, wild-type enzyme, with substrates deoxycytidine and ATP, mixed inhibition Homo sapiens
2.7.1.74 0.05
-
 dCTP pH 7.6, 37°C, wild-type enzyme, with substrates cladribine and UTP, uncompetitive inhibition Homo sapiens
2.7.1.74 0.052
-
 dCTP pH 7.6, 37°C, enzyme mutant S74E, with substrates deoxycytidine and UTP, uncompetitive inhibition Homo sapiens
2.7.1.74 0.398
-
 dCTP pH 7.6, 37°C, wild-type enzyme, with substrates deoxycytidine and UTP, uncompetitive inhibition Homo sapiens

General Information

EC Number General Information Comment Organism
2.7.1.74 additional information deoxycytidine kinase is a key enzyme in the activation of several therapeutic nucleoside analogues Homo sapiens

kcat/KM [mM/s]

EC Number kcat/KM Value [1/mMs-1] kcat/KM Value Maximum [1/mMs-1] Substrate Comment Organism Structure
2.7.1.74 1.8
-
 fludarabine pH 7.6, 37°C, enzyme mutant S74E, with co-substrate ATP Homo sapiens
2.7.1.74 2.6
-
 fludarabine pH 7.6, 37°C, enzyme mutant S74E, with co-substrate UTP Homo sapiens
2.7.1.74 3
-
 fludarabine pH 7.6, 37°C, wild-type enzyme, with co-substrate ATP Homo sapiens
2.7.1.74 6.4
-
 fludarabine pH 7.6, 37°C, wild-type enzyme, with co-substrate UTP Homo sapiens
2.7.1.74 50.1
-
 clofarabine pH 7.6, 37°C, wild-type enzyme, with co-substrate ATP Homo sapiens
2.7.1.74 56.3
-
 clofarabine pH 7.6, 37°C, wild-type enzyme, with co-substrate UTP Homo sapiens
2.7.1.74 57.6
-
 clofarabine pH 7.6, 37°C, enzyme mutant S74E, with co-substrate UTP Homo sapiens
2.7.1.74 74.3
-
 cladribine pH 7.6, 37°C, wild-type enzyme, with co-substrate ATP Homo sapiens
2.7.1.74 76.8
-
 clofarabine pH 7.6, 37°C, enzyme mutant S74E, with co-substrate ATP Homo sapiens
2.7.1.74 90.2
-
 cladribine pH 7.6, 37°C, enzyme mutant S74E, with co-substrate ATP Homo sapiens
2.7.1.74 130
-
 cladribine pH 7.6, 37°C, wild-type enzyme, with co-substrate UTP Homo sapiens
2.7.1.74 136
-
 cladribine pH 7.6, 37°C, enzyme mutant S74E, with co-substrate UTP Homo sapiens
2.7.1.74 236
-
 deoxycytidine pH 7.6, 37°C, wild-type enzyme, with co-substrate ATP Homo sapiens
2.7.1.74 257
-
 deoxycytidine pH 7.6, 37°C, wild-type enzyme, with co-substrate UTP Homo sapiens
2.7.1.74 676
-
 deoxycytidine pH 7.6, 37°C, enzyme mutant S74E, with co-substrate ATP Homo sapiens
2.7.1.74 745
-
 deoxycytidine pH 7.6, 37°C, enzyme mutant S74E, with co-substrate UTP Homo sapiens